Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Hesperetin protects SH-SY5Y cells against 6-hydroxydopamine-induced neurotoxicity via activation of NRF2/ARE signaling pathways

Jing Li¹, Yue Liu¹, Li Wang², Zhaowei Gu¹, Zhigang Huan², Hui Fu², Qishuai Liu²

¹Encephalopathy Center, The 3rd Affiliated Hospital of Changchun University of Chinese Medicine, Changchun City, Jilin Province 130000; ²Department of Nephrology, The First Hospital of ZiBo, Zibo City, Shandong Province 255200, China.

For correspondence:- Qishuai Liu Email: QishuaiLiufjk@163.com Tel:+865334251458

Accepted: 28 May 2020 Published: 30 June 2020

Citation: Li J, Liu Y, Wang L, Gu Z, Huan Z, Fu H, et al. Hesperetin protects SH-SY5Y cells against 6-hydroxydopamine-induced neurotoxicity via activation of NRF2/ARE signaling pathways. Trop J Pharm Res 2020; 19(6):1197-1201 doi: 10.4314/tjpr.v19i6.12

© 2020 The authors.
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Abstract

Purpose: To investigation the protective effects of hesperetin against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity.

Methods: SH-SY5Y cells were incubated with 6-OHDA to create an in vitro model of neurotoxicity. This model was used to test the neuroprotective effects of hesperetin. Cell viability was assessed by MTT and lactate dehydrogenase (LDH) release assays. Flow cytometry and western blot were used to quantify apoptosis. Oxidative stress was evaluated by determining intracellular glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS).

Results: In SH-SY5Y cells, treatment with 6-OHDA decreased cell viability and promoted LDH release. However, exogenous hesperetin protected against 6-OHDA-mediated toxicity. Similarly, although incubation with 6-OHDA induced apoptosis and increased cleaved caspase-3 and -9 levels, treatment with hesperetin protected against these effects. Treatment with 6-OHDA also led to significant oxidative stress, as indicated by reduced GSH and SOD levels and increased MDA and ROS levels in SH-SY5Y cells. However, these changes were reversed by pre-treatment with hesperetin. Of interest, hesperetin led to changes in 6-OHDA-induced expression of NRF2, heme oxygenase-1 (HO-1), glutamate-cysteine ligase (GCL) catalytic subunit (GCLC), and GCL modulatory (GCLM).

Conclusion: Hesperetin protects against cell toxicity, apoptosis, and oxidative stress via activation of NRF2 pathway in a 6-OHDA-induced model of neurotoxicity. Future studies should investigate the use of hesperetin as a potential therapeutic approach for prevention or management of Parkinson’s disease.

Keywords: Hesperetin, 6-OHDA, Neurotoxicity, NRF2, Parkinson's disease